New pathway for DNA damage from nano-particles

Scientists reported Thursday that nano-particles used in medical applications can indirectly damage DNA inside cells by transmitting signals through a protective barrier of human tissue.

The stunning discovery adds to a growing body of research highlighting proven and potential health hazards from the rapidly expanding universe of engineered objects measured in billionths of a metre.

Nano-scale products already widely in use range from cosmetics to household cleaning products to sporting goods.

But the new findings, reported in the British journal Nature Nanotechnology, could also point to new ways in which nano-therapies might zero in on disease-causing tumours, the researchers said.

They could even shed light on how poorly understood pathogens penetrate into human organs.

In laboratory experiments, scientists led by Charles Case of Southmead Hospital in Bristol, Britain, grew a multi-layer "barrier" of human cells to mimic specialised protective tissues found in the body.

One such barrier, for example, separates blood from the brain.

Underneath this layer three-to-four cells thick, they placed human fibroblast cells, which play a key role in the formation of connective and scar tissue.

And on top they put nano-scale particles of cobalt-chromium, an alloy that has long been used in the making of hip- and knee-replacement joints, and more recently in drug-delivery mechanisms used inside arteries.

Earlier studies had shown that direct exposure to large quantities of the alloy could severely damage DNA is some cells, and the researchers wanted to find out how well the lab-grown barrier would protect the fibroblast cells below.

"We never imagined that it wouldn't," Case told journalists by phone.

"But to our great surprise, not only did we see damage on the other side of the barrier, we saw as much damage as if we had not had a barrier at all," he said.

At first, the researchers speculated that the tiny particles -- barely 30 billionth of a meter in diameter -- had slipped through microscopic cracks in the cellular blockade.

But there was no sign of the alloy on the other side, and when the experiment was repeated with far larger particles, the result was essentially the same.

"We could only conclude that the DNA damage occurred after indirect exposure depending on a process of signalling between cells rather than the passage of metal through the barrier," said Gevdeep Bhabra, a surgeon at Southmead and a co-author of the study.

For Jim Thomson of the Canada-based technology watchdog ETC Group, the findings "expand significantly the hurdles that any theoretical nano-safety assessment would need to clear."

His views were echoed by the researchers themselves and experts not involved in the study.

"What it tells me is that the precaution with which some scientists and regulators say we should proceed is the right way to go," said Vyvyan Howard, a pathologist at the University of Ulster who founded the Journal of Nanotoxicology.

But the newly uncovered mechanism holds promise too, these and others experts said.

"The first exciting question is, can we deliver novel therapies across barriers without having to cross them?", said Ashley Blom, an orthopaedic surgeon and professor at the University of Bristol.

"There are also implications as to how nano-particles that we all have in our bodies might act across membranes -- small particles like prions and viruses may use some of these mechanisms.

"This opens up a whole new field of research," he added.

Prion diseases occur when a mutated form of the prion protein runs amok, destroying brain cells.

When considering the safety of nano-particles, one must distinguish between medical and broader industrial applications, said Howard.

New drugs are carefully tested, reducing the chances of widespread harm. And even if nano-delivery and imaging systems turn out not to be risk-free, that does not necessarily mean they shouldn't be used.

"Depending on the kind of disease you have, you will accept some very nasty therapies," such as a chemotherapy for cancer, he said.

"But there is a world of difference between accepting a therapy under informed consent, and involuntary exposure," he added, pointing out most industrial uses are not regulated at all.